Animal models of virus-induced demyelination have relevance to the human disease multiple sclerosis (MS). We are particularly interested in viral infections in which myelin degeneration may be immune-mediated. The most important model of this type is the murine infection with Theiler's virus(TV). Mice infected intracerebrally with the DA strain of TV develop a bifasic illness characterized by a first transient phase of grey matter inflammation and a second chronic phase of white matter disease. Such disease is characterized by well-defined areas of primary demyelination which are in strict temporal and anatomical relation to perivascular mononuclear cell infiltrations. Immunosuppression of infected animals results in the prevention of both inflammatory response and demyelination suggesting that myelin injury is mediated through the host-immune response rather than being produced by primary cytocidal viral activity. We recently demonstrated that different animal strains mount an inflammatory response of different intensity to the infection and that the intensity of demyelination parallels the intensity of inflammation in the various strains. We have also shown that animals infected with attenuated cell-adapted virus develop a slower disease with longer incubation period and that myelin degeneration occurs in a recurrent fashion. In addition we showed that demyelinated spinal cords may be extensively remyelinated by Schwann cells in the infection by attenuated virus. Research goal for the coming year are: 1) To investigate the relation between intensity of the inflammatory response and severity of demyelination especially in regard to the number of macrophages in infiltrates. These studies will be conducted using silica as a blocking agent for macrophages. 2) To investigate the source of Schwann cells which invade and remyelinate affected spinal cords. These studies will be conducted using 3H-thymidine as a marker for proliferating Schwann cells for light and ultrastructural autoradiography. 3) To investigate the distribution of viral antigen in affected spinal cords. Identification of the type of cells infected by virus will help us to understand the possible mechanisms of myelin degeneration i.e., direct viral attack versus immune-mediated injury. These studies will be conducted by using viral antibody tagged with horseradish peroxidase through the linking agent Protein-A.